Imaging and genetic biomarkers for Alzheimer's disease

描述（由申请人提供）：阿尔茨海默病（AD）目前影响超过500万美国人，预计到2050年将影响1500万人。生物标志物是目前诊断和量化潜伏性阿尔茨海默病阶段疾病相关变化的唯一可行方法，在此期间，成功的疾病修饰性治疗干预将实现最大的影响。高通量神经成像和遗传学在促进我们对疾病机制的理解和促进治疗发展方面有着良好的记录。我们的目标是利用前瞻性收集的成像、遗传和基因表达ImaGene数据集开发一种多模式生物标志物AD风险评估工具。我们建议应用先进的成像遗传学统计方法来实现以下三个目标：1)确定一组与ad相关的候选成像和遗传生物标志物；2)选择与AD生物学相关性强的基因表达变量；3)开发和验证一个多模态分类器，能够准确评估一个人未来转化为AD的风险。关键疾病相关途径的发现将从根本上推进我们对阿尔茨海默病的分子和遗传触发因素的理解，并使我们更接近基于基因组的干预和个性化风险评估。

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) presently affects over 5 million Americans and is projected to affect 15 million by 2050. Biomarkers are presently the only feasible approach for diagnosing and quantifying disease-associated changes in the latent AD stage during which a successful disease-modifying therapeutic intervention would realize the greatest impact. High-throughput neuroimaging and genetics have a proven track record for critically advancing our understanding of disease mechanisms and promoting therapeutic development. Our goals are to develop a multimodal biomarker AD risk assessment tool using the prospectively collected imaging, genetic and gene expression ImaGene data set. We propose to apply advanced imaging genetics statistical approaches to achieve the following three aims: 1) identify a discovery set of AD-relevant candidate imaging and genetic biomarkers; 2) select gene expression variables with strong evidence for biological relevance to AD; and 3) develop and validate a multimodal classifier capable of accurately assessing one's risk for future conversion to AD. The discovery of critical disease-related pathways will fundamentally advance our understanding of the molecular and genetic triggers of AD and bring us closer to genomic-based interventions and personalized risk assessment. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health as there is an urgent need for biomarkers capable of early and presymptomatic diagnosis and for discovery of critical disease-associated pathways. The proposed research is highly relevant to the mission of NIA because it will 1) identify and test key imaging and peripheral blood genetic biomarkers that when combined will help diagnose early AD and 2) critically inform AD drug development.